Abstract
Functions of intrinsically disordered proteins do not require structure. Such structure-independent functionality has melted away the classic rigid “lock and key” representation of structure–function relationships in proteins, opening a new page in protein science, where molten keys operate on melted locks and where conformational flexibility and intrinsic disorder, structural plasticity and extreme malleability, multifunctionality and binding promiscuity represent a new-fangled reality. Analysis and understanding of this new reality require novel tools, and some of the techniques elaborated for the examination of intrinsically disordered protein functions are outlined in this review.
Highlights
F1000 Faculty Reviews are written by members of the prestigious F1000 Faculty
In line with this hypothesis were numerous pieces of evidence generated by the crystal structures of proteins solved by x-ray diffraction, careful analysis of protein denaturation and unfolding, and many other observations, all indicating that specific functionality of a given protein is defined by a unique spatial positioning of its amino acid side chains and prosthetic groups, suggesting that such a specific spatial arrangement of functional groups in biologically active proteins is defined by their unique 3D structures predetermined by the unique amino acid sequences encoded in unique genes
intrinsically disordered protein (IDP)/intrinsically disordered protein region (IDPR) are commonly involved in transient protein–protein interactions, which are crucial for cell signalling, characterization of such interactions at the atomicresolution level is rather challenging by the majority of conventional techniques
Summary
F1000 Faculty Reviews are written by members of the prestigious F1000 Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. Computational approaches for the analysis of disorderbased functionality Among the important features of IDPs/IDPRs associated with their functionality are the ability to undergo at least partial folding at interaction with specific partners[5,8,18,44,45,46,47,183,184,185,186,187,188,189] and the capability to bind to multiple partners and gain very different structures in the bound state[190,191,192,193,194,195,196], which increases complexity of the disorder-based interactomes[197]. Abbreviations BiFC, bimolecular fluorescence complementation; coIP, coimmunoprecipitation; ELM, eukaryotic linear motif; FOV, field of view; ID3, IDPR linking the KIX domain and bromodomain of CBP; IDP, intrinsically disordered protein; IDPR, intrinsically disordered protein region; LLPS, liquid–liquid phase separation; LLPT, liquid–liquid phase transition; MoRF, molecular recognition feature; NMR, nuclear magnetic resonance; PDL, proximity-dependent labelling; PMLO, proteinaceous membrane-less organelle; PPI, protein–protein interaction; PSP, phase-separating protein; PTM, post-translational modification; SAXS, small-angle x-ray scattering; SLiM, short linear sequence motif; smFRET single-molecule Förster resonance energy transfer; SPR, surface plasmon resonance; YTH, yeast-two-hybrid
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